Glaucoma is one of the leading causes of irreversible blindness worldwide. Because it is a chronic disease with a long course and is symptomless until the late stages, diagnosis and monitoring are essential to prevent permanent damage to the optic nerve. The National Eye Institute, in its "Vision Research: A National Plan", states that the development of "improved diagnostic techniques encompassing measures of visual function, optic nerve, and nerve fiber layer structure..." are program goals. In seeking better tools for the early diagnosis of glaucoma damage, we propose a new approach based on the assessment of retinal tissue loss at the posterior pole, where there is an abundance of ganglion cells which are essential to central vision and which are lost in glaucoma. We have developed a computerized optical method, the Retinal Thickness Analyzer (RTA), to map the retinal thickness at the posterior pole. Large losses in retinal thickness were detected by the RTA at the posterior pole of glaucoma patients due to the loss of ganglion cells and nerve fibers corresponding to the locations of documented visual field defects. Moreover, retinal thickness loss was found in areas devoid of visual field defects. In accordance with the NEI recommendation, we will use epidemiologic methods to develop reliable, valid criteria for the diagnosis and progression of primary open-angle glaucoma, based on the RTA. The NEI has identified an important research question to be addressed: "what is the relationship between visual function loss and structural changes to the optic nerve and retinal nerve fiber layer in glaucoma?". We propose to investigate the utility of the RTA for diagnosis and monitoring of glaucoma and assess, for the first time, the loss of the central ganglion cells and nerve fibers. We will examine: 1) in a cross-sectional study, whether the RTA can detect decreased retinal thickness, relative to normal thickness, in areas with well documented glaucomatous damage; 2) in a longitudinal study, the characteristics of RTA measurements which precede new visual field loss in established glaucoma patients. In addition, a second promising technology, the GDx Nerve Fiber Analyzer (NFA), a scanning laser polarimeter that measures nerve fiber layer retardation loss in the peripapillary area, will be evaluated and compared with the RTA. In sum, we propose to evaluate and compare the sensitivity, specificity, validity, and reliability of the RTA and the NFA in identifying eyes with glaucoma and in identifying eyes at increased risk of progression of glaucomatous visual field defects. This assessment of the RTA and NFA will help to establish their utility as outcome measures for clinical management of glaucoma, epidemiological research, and clinical trials.